Many methods have been proposed to administer a percutaneous absorption type drug through the skin. The most typical method comprises forming an adhesive layer comprising a polymer which is pressure-adhesive at room temperature, such as natural rubbers, synthetic rubbers and acryl resins, and a percutaneous absorption type drug dispersed in the polymer on one surface of a flexible backing as disclosed in, for example, U.S. Pat. No. 3,632,740.
The amount of the percutaneous absorption type drug present in those conventional preparations is over a wide range. Usually, however, as disclosed in U.S. Pat. No 3,632,740, particularly the examples therein, the practical amount of the drug present is equal to or below the saturated solubility thereof in the polymer. The reason for this is even if drug is added in an amount greater than the saturated solubility in the polymer, the excess amount above the saturated solubility is present in the polymer in the form of large-sized crystalline particles and thus does not contribute any pharmacological action, viz., it remains on the adhesive layer without being absorbed through the skin.
Several methods have been employed to increase the amount of a drug absorbed through the skin, i.e., the dose of the drug.
One of these methods comprises increasing the thickness of the adhesive layer containing the drug or increasing the size of the preparation. This method, however, is not satisfactory because it is not economical and furthermore gives a feeling of physical discomfort to the user.
As modifications of the above structure, a preparation comprising a backing, an adhesive layer, and a drug reservoir layer (in combination with a drug release rate controlling membrane) is disclosed in, for example, U.S. Pat. Nos. 3,598,122 and 3,598,123. The reservoir layer is composed of a bag or microcapsules with a drug-permeable wall.
The drug present in the reservoir layer is released continuously through the wall, diffuses into the pressure-sensitive adhesive layer adjacent the reservoir layer and is finally administered continuously through the skin or mucosa to which the preparation has been applied. A controlling layer is interposed between the adhesive layer and the reservoir layer and functions to control the release of the drug to the adhesive layer. A preparation of this type has the advantage that the drug can be incorporated regardless of the saturated solubility thereof in the pressure-sensitive adhesive. However, much labor and great costs are required to select the combination of the wall material, the controlling membrane and the drug.
A laminate type preparation comprising a backing layer, a drug reservoir layer, a microporous membrane layer and a contact-adhesive layer, wherein the adhesive layer contains large drug particles in an undissolved state is also disclosed in, for example, U.S. Pat. No. 4,201,211.
The adhesive layer in this preparation is prepared by mixing an inert liquid in which a drug has a low solubility, an adhesive component such as polyisobutylene, and drug particles under conditions such that a high shearing force is exerted on the drug particles to thereby prepare a mixture containing drug particles in a suspended state and then coating the mixture.
In an adhesive layer prepared by coating a liquid containing drug particles suspended in the adhesive component, since the drug particles are not dissolved in the system, the particles are often dispersed non-uniformly in the adhesive layer. As a result, the release of the drug becomes non-uniform. Furthermore, due to the particle size of the drug crystals, it is difficult to form an adhesive layer having a uniform and thin thickness. In particular, the thickness of the adhesive layer cannot be decreased to below the drug particle size since the particles prevent the formation of an adhesive layer having a smooth adhesive layer surface and an adhesive layer, which does not have a smooth layer surface, does not have a satisfactory appearance and also from the standpoint of pharmaceutical effect, the preparation does not have a uniform drug releasing surface.